Cargando…

miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics

BACKGROUND: The tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively r...

Descripción completa

Detalles Bibliográficos
Autores principales: Bar, Nadav, Dikstein, Rivka
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877705/
https://www.ncbi.nlm.nih.gov/pubmed/20523723
http://dx.doi.org/10.1371/journal.pone.0010859
_version_ 1782181803246747648
author Bar, Nadav
Dikstein, Rivka
author_facet Bar, Nadav
Dikstein, Rivka
author_sort Bar, Nadav
collection PubMed
description BACKGROUND: The tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively regulated by AKT-mediated phosphorylation. PTEN activity is frequently lost in many types of cancer, leading to increased cell survival and cell cycle progression. PRINCIPAL FINDINGS: Here we characterize the widely expressed miR-22 and report that miR-22 is a novel regulatory molecule in the PTEN/AKT pathway. miR-22 downregulates PTEN levels acting directly through a specific site on PTEN 3′UTR. Interestingly, miR-22 itself is upregulated by AKT, suggesting that miR-22 forms a feed-forward circuit in this pathway. Time-resolved live imaging of AKT-dependent FoxO1 phosphorylation revealed that miR-22 accelerated AKT activity upon growth factor stimulation, and attenuated its down regulation by serum withdrawal. CONCLUSIONS: Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway.
format Text
id pubmed-2877705
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-28777052010-06-03 miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics Bar, Nadav Dikstein, Rivka PLoS One Research Article BACKGROUND: The tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively regulated by AKT-mediated phosphorylation. PTEN activity is frequently lost in many types of cancer, leading to increased cell survival and cell cycle progression. PRINCIPAL FINDINGS: Here we characterize the widely expressed miR-22 and report that miR-22 is a novel regulatory molecule in the PTEN/AKT pathway. miR-22 downregulates PTEN levels acting directly through a specific site on PTEN 3′UTR. Interestingly, miR-22 itself is upregulated by AKT, suggesting that miR-22 forms a feed-forward circuit in this pathway. Time-resolved live imaging of AKT-dependent FoxO1 phosphorylation revealed that miR-22 accelerated AKT activity upon growth factor stimulation, and attenuated its down regulation by serum withdrawal. CONCLUSIONS: Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway. Public Library of Science 2010-05-27 /pmc/articles/PMC2877705/ /pubmed/20523723 http://dx.doi.org/10.1371/journal.pone.0010859 Text en Bar, Dikstein. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bar, Nadav
Dikstein, Rivka
miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics
title miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics
title_full miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics
title_fullStr miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics
title_full_unstemmed miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics
title_short miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics
title_sort mir-22 forms a regulatory loop in pten/akt pathway and modulates signaling kinetics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877705/
https://www.ncbi.nlm.nih.gov/pubmed/20523723
http://dx.doi.org/10.1371/journal.pone.0010859
work_keys_str_mv AT barnadav mir22formsaregulatoryloopinptenaktpathwayandmodulatessignalingkinetics
AT diksteinrivka mir22formsaregulatoryloopinptenaktpathwayandmodulatessignalingkinetics